47 research outputs found
Venetoclax–Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia
Background: Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia.
Methods: In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax–rituximab group) or bendamustine plus rituximab for 6 months (bendamustine–rituximab group). The trial design did not include crossover to venetoclax plus rituximab for patients in the bendamustine–rituximab group in whom progression occurred. The primary end point was investigator-assessed progression-free survival.
Results: After a median follow-up period of 23.8 months, the rate of investigator-assessed progression-free survival was significantly higher in the venetoclax–rituximab group (32 events of progression or death in 194 patients) than in the bendamustine–rituximab group (114 events in 195 patients); the 2-year rates of progression-free survival were 84.9% and 36.3%, respectively (hazard ratio for progression or death, 0.17; 95% confidence interval [CI], 0.11 to 0.25; P<0.001 by the stratified log-rank test). The benefit was maintained across all clinical and biologic subgroups, including the subgroup of patients with chromosome 17p deletion; the 2-year rate of progression-free survival among patients with chromosome 17p deletion was 81.5% in the venetoclax–rituximab group versus 27.8% in the bendamustine–rituximab group (hazard ratio, 0.13; 95% CI, 0.05 to 0.29), and the 2-year rate among those without chromosome 17p deletion was 85.9% versus 41.0% (hazard ratio, 0.19; 95% CI, 0.12 to 0.32). The benefit of venetoclax plus rituximab over bendamustine plus rituximab was confirmed by an independent review committee assessment of progression-free survival and other secondary efficacy end points. The rate of grade 3 or 4 neutropenia was higher in the venetoclax–rituximab group than in the bendamustine–rituximab group, but the rates of grade 3 or 4 febrile neutropenia and infections or infestations were lower with venetoclax than with bendamustine. The rate of grade 3 or 4 tumor lysis syndrome in the venetoclax–rituximab group was 3.1% (6 of 194 patients).
Conclusions: Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progression-free survival than bendamustine plus rituximab. (Funded by Genentech and AbbVie; ClinicalTrials.gov number, NCT02005471.
The urgent need for integrated science to fight COVID-19 pandemic and beyond
The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health
concern is not only a medical problem, but also afects society as a whole; so, it has also become the leading scientifc
concern. We discuss in this treatise the importance of bringing the world’s scientists together to fnd efective solu‑
tions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to
manage the pandemic’s consequences and prevent recurrences of similar pandemics
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Survival for patients with invasive cutaneous melanoma among ethnic groups: the effects of socioeconomic status and treatment.
Although uncommon, melanoma is associated with poor survival characteristics among African Americans and Hispanics compared with non-Hispanic whites (NHWs). Low socioeconomic status (SES) is also associated with poor survival among patients with melanoma, but it is not known whether this is because of SES itself or because of treatment disparities. We set out to determine this by using the large, population-based California Cancer Registry (CCR) database as a model.We conducted a case-only analysis of CCR data (1993 to 2003), including a descriptive analysis of relevant clinical variables and SES. The SES variable used has been derived from principle component analysis of census block-level CCR data that was linked to census data to address seven indicators of SES. Univariate analyses of overall survival (OS) were conducted using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazard ratios (HRs).A total of 39,049 incident patient cases of cutaneous melanoma, including 36,694 in NHWs; 127 in African Americans; 1,996 in Hispanics; and 262 in Asian-Americans, were analyzed. Higher SES was associated with an early stage at presentation (P < .0001), with treatment with surgery (P = .0005), and with prolonged survival (P < .0001). After adjustments for age, sex, histology, American Joint Committee on Cancer stage, anatomic site, treatment, and SES, a statistically significant increased risk of death was observed for African Americans compared with NHWs (HR, 1.60; 95% CI, 1.17 to 2.18); no survival differences were noted for Asians or Hispanics compared with NHWs in the adjusted analysis.Low SES independently predicts poor outcome among patients with cutaneous melanoma. However, the poor OS observed for African American patients with melanoma is not explained by differences in treatment or SES
Feasibility and implementation of geriatric assessment measures and patient-reported outcomes in a phase 1 trial for acute myeloid leukemia.
Multicenter, phase III, open-label, randomized study in relapsed/refractory CLI, to evaluate the benefit of GDC-0199 (ABT-199) plus rituximah compared with bendamustine plus rituximab.
Multicenter, phase III, open-label, randomized study in relapsed/refractory CLL to evaluate the benefit of GDC-0199 (ABT-199) plus rituximab compared with bendamustine plus rituximab.
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CD68+ tumor-associated myeloid cells as the target of adenosine-induced gene products and predictor of response to adenosine blockade with ciforadenant (cifo) in renal cell cancer (RCC)
5025 Background: Adenosine in the tumor microenvironment (TME) is immunosuppressive and may play a role in resistance to immunotherapy. We described an adenosine induced gene expression signature (AS, Fong, Cancer Disc 2020) that correlates with response to therapy with cifo, an adenosine A2A receptor antagonist, as monotherapy or in combination with atezolizumab in refractory RCC. These genes express chemokines that signal through CCR2 and CXCR2 to recruit myeloid cells including immunosuppressive tumor associated-M2 macrophages, which are thought to mediate resistance to anti-PD(L)1 treatment. We now identify tumor infiltrating CD68+ myeloid cells as the effector cell for adenosine mediated immunosuppression. Methods: 82 RCC pts have been treated in an ongoing Phase 1/1b trial evaluating cifo (100mg po bid) monotherapy or combination with atezolizumab (840mg IV q 2 weeks). Tumor biopsies, obtained at screening and on therapy, are available for analysis in 32 pts to date. RNA expression was measured in tumors using Nanostring. Immunohistochemistry (IHC) for CD68 was performed on biopsies with CD68+ tumors defined as > 4% tumor area containing CD68+ cells. Results: Pt characteristics are median age 63; median prior therapies 3, with 72% failing prior anti-PD(L)1. Gene expression of M2 markers consisting of CD68 (p = 0.0008) and CD163 (p = 0.03) was higher in baseline samples from AS+ compared to AS- pts. By IHC, 10 pts had CD68+ cells infiltrating the tumor; 9 of 10 AS+. Tumor regression was observed in 6 of 10 CD68+ pts (N = 3 monotherapy and 3 combination) including 4 partial responses (PR, RECIST). No PRs and 2 minor responses were seen in 22 pts who were CD68- (p < 0.005). Median time to progression was not reached for CD68+ vs 2 mo for CD68-. Paired biopsies showed a significant reduction in infiltrating CD68+ cells (p = 0.03) with treatment including 2 of 2 evaluable PRs. Conclusions: Adenosine immunosuppression is mediated by M2 macrophages, which can be reversed by cifo. Enumerating tumor infiltrating CD68+ cells may be a valuable biomarker for identifying pts that will respond to adenosine blockade. Clinical trial information: NCT02655822